This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The dorsomedial hypothalamus (DMH) plays an important role in coordinating neuroendocrine, autonomic, and behavioral responses to stress-related stimuli. In vertebrates, DMH serotonin (5-HT) concentrations are rapidly increased in response to acute stressors or corticosterone (CORT) administration. The mechanisms underlying 5-HT accumulation in the DMH are not clear, but our previous data support the hypothesis that CORT inhibits postsynaptic uptake and therefore clearance of 5-HT from the extracellular fluid via inhibition of organic cation transporter 3- (OCT3), a polyspecific CORT-sensitive transport protein. Within the DMH, OCT3 is expressed by neurons and glial cells in the parenchyma, and ependymal cells lining the third ventricle. Because OCTs are low-affinity, high-capacity transporters, we predict that CORT effects on extracellular 5-HT would be most pronounced in the presence of elevated 5-HT activity.
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